Beating Stress, Anxiety and Depression by Inhibiting Substance P

A man wearing a facemask with a skeptical look on his face sits at his kitchen table holding his laptop in one hand and a glass of wine in the other

Social isolation that goes too long is associated with this molecule of Tachykinin in everything from flies to humans. It makes us more irritable, fearful, paranoid, and impairs our immune system.

Tachykinin is like this internal punishment signal. It’s like our body and our brain telling us, “You’re not spending enough time with people that you really trust. You’re not spending time doing things that you really enjoy.

Having a sense of delight, a sense of really enjoying something that you see and engage in, witness, or participate in, that is associated with the serotonin system. And certainly, play is one of those things.

Dr. Andrew Huberman

I’ve written a number of posts on improving emotional welfare, and how it can shape immune system and physical functioning. Some specific topics include how to find a balance in your life, the pitfalls of the self-absorption paradox, and how interpersonal communication is implicated in mental state, emotions and motivation.

Prolonged stress and anxiety can lead to major depression, and two conditions that cause elevated stress and anxiety are self-isolation and burnout from overworking without downtime to recharge.

Fortunately, it’s easy to take measures that modulate the hormones and neurotransmitters implicated in these mental states, which I’ll discuss more at length in this post.

The benefits of social connection on mental welfare are pretty well publicized, and rightly so, but one thing I’ve recently discovered for myself (and about the human condition) is that it’s really about just getting out and experiencing life.

How Long-Term Stress Can Create Major Depression

When we are chronically-stressed, we get inflamed. Various cells in the brain become inflamed, and their communication with the neurons of the brain and body is disrupted.

So, what specifically is creating chronic inflammation in the brain?

It’s caused by signaling proteins known as inflammatory cytokines.

The primary function of these molecules is to inhibit the release or synthesis of serotonin, norepinephrine, and dopamine—all the neurotransmitters that allow you to feel happy, relaxed and motivated.

I’ll spare you the technical names and details of these, since, in full disclosure, I’m not sure what the functions of and distinctions between them all are, myself. But, there is one molecule I want to discuss, that goes by the name Tachykinin, also know as substance P.

The Sinister Nature of Tachykinin (Substance P)

The neurotransmitter Tachykinin, leads to the production of these inflammatory cytokines. Its receptors are found in brain areas implicated in stress-mechanisms, mood/anxiety regulation and emotion-processing. It is released from sensory neurons of damaged tissue during the neurogenic inflammation response, which as you probably can guess, occurs between the nervous system and the immune system.

Substance P plays a role in many critical physiological processes like the immune response (the inflammation component), pain perception, circulation and respiration, and gastrointestinal functioning (digestion).

Thus, when unchecked, it can worsen or lead to many physical ailments, including intestine and urinary bladder disorders, infection, chronic inflammation and arthritis, diabetes, heart disease and cancer.

But, more relevant to this post, it can greatly influence various mental processes, and lead to the development of psychological conditions, including anxiety, addictive and affective (depression and bipolar) disorders, schizophrenia, and general irritability. It also can have detrimental effects on memory processing and sleep.

There certainly isn’t much literature on substance P out there for the layman—essentially every article I came across was a peer-reviewed study.

But from what I was able to dig up, the way I understand it is that due to it’s prevalence in the body and its neuromodulatory effects, it can have dramatic influence on the development and mitigation of depression and anxiety, specifically social phobia.

Courtesy of Science Direct

The ironic thing is that it seems to be a hamster wheel cycle. Elevated circulating substance P caused you to become more fearful of social interaction, and the more you hide away, the more you increase tachykinin production—and vice versa.

Specific Methods for Suppressing Tachykinin

So, after taking all this into account, it appears evident that social connection is the most logical tactic you can use to sequester substance P, and facilitate improvements in depression, anxiety, and general mental wellbeing. Assuming, of course a tachykinin imbalance is what ails your mood.

But, I know for me personally, just getting out and interacting with people on the street can turn my whole day around. In my case, it helps to do it early before the stresses of work have wore down my aura for the sake of reciprocity from others. But even in the evening, nine times out of ten my wellbeing is so much better off when I return home.

The other effective technique, especially when used in tandem with the first, is to just have more downtime removed from the stresses of work, where you engage in past times you enjoy.

For me, one such delight-invoking activity is skateboarding. I just feel in my element when I’m on my board, even if just cruising the street. But when I’m at the park, in nature, surrounded by other skaters’ company I enjoy, it can be like a state of ecstasy.

Add the fact it’s aerobic, load-bearing exercise, and this is the ultimate mental state-boosting triple-whammy.

The other thing that makes me feel whole and boosts my serotonin is DJing. And when I lived in Chicago and could do it with my partner, it was even more blissful and fulfilling.

I definitely enjoy doing it in the comfort of my own home, but getting out and spinning in public is that much better. It’s certainly has something to do with the social interaction, bonding-over-music component—and that’s often the subject matter in the music I play out.

That’s one of the big things I like about music to begin with; it’s enchanting because it can bring people from all walks of life – who may not even speak the same language – together.

Having someone approach you to ask the name of a track, or better yet, flailing uncontrollably around while freaking out on the dancefloor is one of the most gratifying events I’ve experienced.

I’m fairly certain you know the feeling I’m talking about, and what that thing is for you that makes you feel it. It may have gotten away from you with all the perceptual stimulation we’re constantly facing.

But with a little searching and time removed from distractions where you can just think should help you remember what it was. And when you can reconnect with it, it definitely will help you mitigate substance P and elevate your mood.

Probably for some, the social interaction aspect not quite to the same effect. But still, combining these two should go a long way in alleviating social anxiety and depression, and may even improve your immune system.

– CC


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